Hachisu M, Pappano A J
J Pharmacol Exp Ther. 1983 Apr;225(1):112-20.
The electrophysiological and chemical properties of the Ca++-channel blocking drugs verapamil, nifedipine and nimodipine were compared. In avian ventricular muscle depolarized by 25 mM K+-saline, the primary Na+ conductance was inactivated and the peak of action potential varied by 30 mV/10-fold change in extracellular Ca++. A double reciprocal plot of the maximum rate of rise vs. [Ca++]0(-1) yielded a straight line, a result consistent with the surface density hypothesis for the electrogenic permeation of cell membranes by Ca++. Verapamil, nifedipine and nimodipine caused the peak of action potential to deviate significantly from its Ca++-electrode property. Verapamil, but not nifedipine or nimodipine, blocked the Ca++-dependent action potential in a frequency-dependent manner. However, the dihydrophyridines (nifedipine and nimodipine) and verapamil were similar insofar as they inhibited the maximum rate of rise of the Ca++-dependent action potential competitively at concentrations less than or equal to 10(-6) M. These results are consistent with the hypothesis that low concentrations of these drugs inhibit the Ca++-dependent action potential by reducing the secondary inward current which is carried largely by Ca++. At higher concentrations, blockade of the maximum rate of rise by all of the Ca++-channel blocking drugs could not be described as competitive, noncompetitive or uncompetitive. The inability to describe the equilibrium actions of high concentrations of verapamil, nifedipine and nimodipine in such terms may arise from drug effects on membrane currents in addition to secondary inward current.
比较了钙离子通道阻滞剂维拉帕米、硝苯地平和尼莫地平的电生理和化学性质。在由25 mM钾盐溶液去极化的禽类心室肌中，主要的钠离子电导失活，动作电位峰值随细胞外钙离子浓度每10倍变化而改变30 mV。最大上升速率与[Ca++]0(-1)的双倒数图得到一条直线，这一结果与细胞膜通过钙离子进行电渗的表面密度假说一致。维拉帕米、硝苯地平和尼莫地平使动作电位峰值显著偏离其钙离子电极特性。维拉帕米以频率依赖性方式阻断钙离子依赖性动作电位，而硝苯地平和尼莫地平则无此作用。然而，二氢吡啶类药物（硝苯地平和尼莫地平）和维拉帕米在浓度小于或等于10(-6) M时，都能竞争性抑制钙离子依赖性动作电位的最大上升速率，在这方面它们是相似的。这些结果与以下假说一致：低浓度的这些药物通过减少主要由钙离子携带的次级内向电流来抑制钙离子依赖性动作电位。在较高浓度时，所有钙离子通道阻滞剂对最大上升速率的阻断不能用竞争性、非竞争性或非竞争性来描述。无法用这些术语描述高浓度维拉帕米、硝苯地平和尼莫地平的平衡作用，可能是由于药物除了对次级内向电流有影响外，还对膜电流有作用。
